Correction for founder effects in host-viral association studies via principal components

Viruses such as HIV and Hepatitis C (HCV) replicate rapidly and with high transcription error rates, which may facilitate their escape from immune detection through the encoding of mutations at key positions within human leukocyte antigen (HLA)-specific peptides, thus impeding T-cell recognition. Large-scale population-based host-viral association studies are conducted as hypothesis-generating analyses which aim to determine the positions within the viral sequence at which host HLA immune pressure may have led to these viral escape mutations. When transmission of the virus to the host is HLA-associated, however, standard tests of association can be confounded by the viral relatedness of contemporarily circulating viral sequences, as viral sequences descended from a common ancestor may share inherited patterns of polymorphisms, termed 'founder effects'. Recognizing the correspondence between this problem and the confounding of case-control genome-wide association studies by population stratification, we adapt methods taken from that field to the analysis of host-viral associations. In particular, we consider methods based on principal components analysis within a logistic regression framework motivated by alternative formulations in the Frisch-Waugh-Lovell Theorem. We demonstrate via simulation their utility in detecting true host-viral associations whilst minimizing confounding by associations generated by founder effects. The proposed methods incorporate relatively robust, standard statistical procedures which can be easily implemented using widely available software, and provide alternatives to the more complex computer intensive methods often implemented in this area

Impact of anti-retroviral therapy and pneumocystis carinii pneumonia prophylaxis on the pattern of AIDS illnesses and AIDS survival in the Western Australian HIV Cohort Study: 1983 - 1992

OBJECTIVE: To evaluate the impact of antiretroviral therapy (ART) and Pneumocystis prophylaxis use on (a) the incidence of Pneumocystis carinii pneumonia (PCP) and CD4+ T-cell counts at AIDS, (b) the patterns of AIDS illnesses and (c) survival after AIDS. DESIGN: Prospective, longitudinal, observational study of all 230 patients diagnosed with AIDS in Western Australia to 1 January 1993. RESULTS: Of 230 patients with AIDS, 74 (32%) had begun both ART and PCP prophylaxis before AIDS and 135 (59%) had received neither therapy before AIDS. Patients treated with ART and PCP prophylaxis were less likely than untreated patients to have PCP as the first AIDS diagnosis (treated 28% versus non-treated 60%, p = 0.0001 Fisher's exact test) and once this was taken into account were also less likely to have Kaposi's sarcoma (KS) (17% versus 42.5%, p = 0.0003). Following adjustment for the reduction in PCP and KS the distribution of other AIDS illnesses was similar in the treated and untreated groups. In multivariate models treatment with ART and PCP prophylaxis before AIDS was associated with reduction in PCP as the first AIDS illness (p Acquired Immunodeficiency Syndrome/*DRUG THERAPY/IMMUNOLOGY/ MORTALITY Antiviral Agents/*THERAPEUTIC USE Australia/EPIDEMIOLOGY AIDS-Related Opportunistic Infections/COMPLICATIONS/*PREVENTION & CONTROL Cohort Studies CD4 Lymphocyte Count Human Longitudinal Studies Pneumonia, Pneumocystis carinii/COMPLICATIONS/*PREVENTION & CONTROL Prospective Studies Survival Rate

Quantum control theory and applications: A survey

This paper presents a survey on quantum control theory and applications from a control systems perspective. Some of the basic concepts and main developments (including open-loop control and closed-loop control) in quantum control theory are reviewed. In the area of open-loop quantum control, the paper surveys the notion of controllability for quantum systems and presents several control design strategies including optimal control, Lyapunov-based methodologies, variable structure control and quantum incoherent control. In the area of closed-loop quantum control, the paper reviews closed-loop learning control and several important issues related to quantum feedback control including quantum filtering, feedback stabilization, LQG control and robust quantum control.Comment: 38 pages, invited survey paper from a control systems perspective, some references are added, published versio

Low acoustic transmittance through a holey structure

J. S. Bell, I. R. Summers, A. R. J. Murray, Euan Hendry, J. Roy Sambles, and Alastair P. Hibbins, Physical Review B, Vol. 85, article 214305 (2012). Copyright © 2012 by the American Physical Society.The “acoustic double fishnet” is a structure with holes running from its front to back faces, yet at a characteristic frequency it transmits very little sound. The transmittance of this structure, which is comprised of a pair of closely spaced, periodically perforated plates, is determined experimentally and analytically. The surprising acoustic properties are due to hybridization between a two-dimensional resonance within the gap between the plates, and pipe modes within the holes. At the center of the stop band the input impedance is imaginary, interpreted as a negative product of effective bulk modulus and density

Electric/Magnetic Duality with Gauge Singlets

We demonstrate how gauge singlets can be used to find new examples of Kutasov duality (i.e. where the matching of the dual theories relies on a non-zero superpotential) in N}=1 SU(N) SQCD with F_Q flavours of quark and multiple generations of adjoints, or antisymmetrics, or symmetrics. The role of the singlets is to simplify greatly the truncation of the chiral ring whilst maintaining an R-symmetry, and at the same time allowing an unambiguous identification of the elementary mesons of the magnetic theory. The dual theories satisfy all the usual tests, including the highly non-trivial 't Hooft anomaly matching conditions.Comment: 31 pages, 2 figure

Towards Supergravity Duals of Chiral Symmetry Breaking in Sasaki-Einstein Cascading Quiver Theories

We construct a first order deformation of the complex structure of the cone over Sasaki-Einstein spaces Y^{p,q} and check supersymmetry explicitly. This space is a central element in the holographic dual of chiral symmetry breaking for a large class of cascading quiver theories. We discuss a solution describing a stack of N D3 branes and M fractional D3 branes at the tip of the deformed spaces.Comment: 28 pages, no figures. v2: typos, references and a note adde

Obstructions to the Existence of Sasaki-Einstein Metrics

We describe two simple obstructions to the existence of Ricci-flat Kahler cone metrics on isolated Gorenstein singularities or, equivalently, to the existence of Sasaki-Einstein metrics on the links of these singularities. In particular, this also leads to new obstructions for Kahler-Einstein metrics on Fano orbifolds. We present several families of hypersurface singularities that are obstructed, including 3-fold and 4-fold singularities of ADE type that have been studied previously in the physics literature. We show that the AdS/CFT dual of one obstruction is that the R-charge of a gauge invariant chiral primary operator violates the unitarity bound.Comment: 35 pages, 1 figure; references and a footnote adde

Dibaryon Spectroscopy

The AdS/CFT correspondence relates dibaryons in superconformal gauge theories to holomorphic curves in Kaehler-Einstein surfaces. The degree of the holomorphic curves is proportional to the gauge theory conformal dimension of the dibaryons. Moreover, the number of holomorphic curves should match, in an appropriately defined sense, the number of dibaryons. Using AdS/CFT backgrounds built from the generalized conifolds of Gubser, Shatashvili, and Nekrasov (1999), we show that the gauge theory prediction for the dimension of dibaryonic operators does indeed match the degree of the corresponding holomorphic curves. For AdS/CFT backgrounds built from cones over del Pezzo surfaces, we are able to match the degree of the curves to the conformal dimension of dibaryons for the n'th del Pezzo surface, n=1,2,...,6. Also, for the del Pezzos and the A_k type generalized conifolds, for the dibaryons of smallest conformal dimension, we are able to match the number of holomorphic curves with the number of possible dibaryon operators from gauge theory.Comment: 30 pages, 6 figures, corrected refs; v3 typos correcte

Does the extended Glasgow Outcome Scale add value to the conventional Glasgow Outcome Scale?

The Glasgow Outcome Scale (GOS) is firmly established as the primary outcome measure for use in Phase III trials of interventions in traumatic brain injury (TBI). However, the GOS has been criticized for its lack of sensitivity to detect small but clinically relevant changes in outcome. The Glasgow Outcome Scale-Extended (GOSE) potentially addresses this criticism, and in this study we estimate the efficiency gain associated with using the GOSE in place of the GOS in ordinal analysis of 6-month outcome. The study uses both simulation and the reanalysis of existing data from two completed TBI studies, one an observational cohort study and the other a randomized controlled trial. As expected, the results show that using an ordinal technique to analyze the GOS gives a substantial gain in efficiency relative to the conventional analysis, which collapses the GOS onto a binary scale (favorable versus unfavorable outcome). We also found that using the GOSE gave a modest but consistent increase in efficiency relative to the GOS in both studies, corresponding to a reduction in the required sample size of the order of 3–5%. We recommend that the GOSE be used in place of the GOS as the primary outcome measure in trials of TBI, with an appropriate ordinal approach being taken to the statistical analysis

Dynamical Fine Tuning in Brane Inflation

We investigate a novel mechanism of dynamical tuning of a flat potential in the open string landscape within the context of warped brane-antibrane inflation in type IIB string theory. Because of competing effects between interactions with the moduli stabilizing D7-branes in the warped throat and anti-D3-branes at the tip, a stack of branes gives rise to a local minimum of the potential, holding the branes high up in the throat. As branes successively tunnel out of the local minimum to the bottom of the throat the potential barrier becomes lower and is eventually replaced by a flat inflection point, around which the remaining branes easily inflate. This dynamical flattening of the inflaton potential reduces the need to fine tune the potential by hand, and also leads to successful inflation for a larger range of inflaton initial conditions, due to trapping in the local minimum.Comment: 23 pages, 9 figures. v2: Updated D3-dependence in potential, small changes to numerical result